pierre.cochat@chu-lyon.fr
Centre de référence des
maladies rénales rares

Université de Lyon

Kidney transplantation in ch...
The very first kidney transplantation in humans
has been performed in

A.
B.
C.
D.
E.

Mumbai, India, 1915
Chicago, USA, 1...
Pig-to-man kidney transplantation…
Vascular anastomosis to the humeral vessels!

Jaboulay Lyon Medical 1906
The first kidney transplantation in humans has
been performed in

A.
B.
C.
D.
E.

Mumbai, India, 1915
Chicago, USA, 1912
M...
What is the lower age limit for kidney Tx?

A.
B.
C.
D.
E.

Birth
6 months
1 year
2 years
3 years
Indication for kidney transplantation
 Children with irreversible renal failure
 Minimal age: 6 to 12 mos
 Minimal BW: ...
Options according to age at start of RRT

Age
PD
HD
Tx

Premature baby – Birth – 6 mos – 12 mos – 18 mos – 2 yrs
Transplantation
6 mos – 5.4 kg

RRT options
1st yr of life

Hemodialysis
5 mos – 4.8 kg
Peritoneal dialysis
1000 g
NAPRTCS 2010
What is the lower age limit for kidney Tx?

A.
B.
C.
D.
E.

Birth
6 months
1 year
2 years
3 years
What is the part of pediatrics among all kidney Tx?

A.
B.
C.
D.
E.

1%
2.5%
5%
7.5%
10%
Kidney transplantation activity in Europe
Cochat Comprehensive Pediatric Nephrology 2008

Country

Total Nb of Tx

Tx in c...
What is the part of pediatrics among all kidney Tx?

A.
B.
C.
D.
E.

1%
2.5%
5%
7.5%
10%
What is the main cause of ESRD in children < 5 yrs?

A.
B.
C.
D.
E.

CAKUT
Steroid resistant nephrotic syndrome
Inherited ...
Wühl Clin J Am Soc Nephrol 2013
What is the main cause of ESRD in children < 5 yrs?

A.
B.
C.
D.
E.

CAKUT
Steroid resistant nephrotic syndrome
Inherited ...
What are the 2 critically important outcomes in
kidney Tx?

A.
B.
C.
D.
E.

Patient survival
Blood pressure
Graft survival...
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

ERA-EDTA ERBP in press
What are the 2 critically important outcomes in
kidney Tx?

A.
B.
C.
D.
E.

Patient survival
Blood pressure
Graft survival...
Preemptive kidney Tx

A.
B.
C.
D.
E.

Is used for an average 25% of the pediatric population
Is associated with a greater ...
% Preemptive Tx in Europe
Cochat Comprehensive Pediatric Nephrology 2008

Sweden
Norway
Netherlands
USA
UK
Spain
Croatia
F...
Transplant characteristics in USA NAPRTCS 2007
The best option for RRT in children is preemptive Tx
Dialysis should be limited to those children who cannot benefit from ...
Preemptive kidney Tx

A.
B.
C.
D.
E.

Involves an average 25% of the pediatric population
Is associated with a greater ris...
In Europe, the average rate of living donation for
children is

A.
B.
C.
D.
E.

15%
20%
25%
30%
40%
% Living (related) donors in pediatric kidney Tx
Cochat Comprehensive Pediatric Nephrology 2008

100
80
60
40
20

Sw USA
i...
In Europe, the rate of living donation for children is

A.
B.
C.
D.
E.

15%
20%
25%
30%
40%
In the post-operative period after cadaver Tx,

A.
B.
C.
D.
E.

The use of 20% mannitol is recommended
The use of dopamine...
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

ERA-EDTA ERBP in press
In the post-operative period after cadaver Tx,

A.
B.
C.
D.
E.

The use of 20% mannitol is recommended
The use of dopamine...
The current rate of acute rejection in kidney Tx is:

A.
B.
C.
D.
E.

3%
13%
23%
33%
43%
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

N

Transplants with
TheatissueRejection
of ARE
Least 1

N

%

...
The current rate of acute rejection in kidney Tx is:

A.
B.
C.
D.
E.

3%
13%
23%
33%
43%
In children, the main cause of graft failure is:

A.
B.
C.
D.
E.

Vascular thrombosis
Recurrence of the primary disease
Ac...
NAPRTCS 2007
In children, the main cause of graft failure is:

A.
B.
C.
D.
E.

Vascular thrombosis
Recurrence of the primary disease
Ac...
In children, the risk of metabolic syndrome at 1 yr
post-Tx is:

A.
B.
C.
D.
E.

5 to 10%
15 to 20%
25 to 30%
35 to 40%
45...
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

Metabolic syndrome in children after renal Tx

 Reversal of m...
In children, the risk of metabolic syndrome at 1 yr
post-Tx is:

A.
B.
C.
D.
E.

5 to 10%
15 to 20%
25 to 30%
35 to 40% wi...
In children, the risk of metabolic syndrome at 1 yr
post-Tx is:

A.
B.
C.
D.
E.

5 to 10% without corticosteroids
15 to 20...
Antibody-mediated rejection

A.
B.
C.
D.
E.

Is associated with serum donor-specific antibodies
Can be treated by high-dos...
Humoral [antibody-mediated] rejection
Diagnosis

Circulating anti-HLA Ab

Protocol biopsy (C4d)

Graft dysfunction
Post...
Pathology

Pericapillary inflammation

Courtesy Dr F Dijoud Lyon 2011

C4d+ on peritubular capillaries
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

Impact of donor-specific anti-HLA antibodies

FO
CUS O RENAL T...
Antibody-mediated rejection

A.
B.
C.
D.
E.

Is associated with serum donor-specific antibodies
Can be treated by high-dos...
In children, these diseases have a 80 to 100% risk
of recurrence in the renal graft

A.
B.
C.
D.
E.

Focal segmental glome...
Recurrent renal diseases: an overview
Recurrence of the full primary renal disease
High risk of graft loss

Low risk of gr...
Recurrence rate after the 1st renal Tx

Primary disease

Recurrence rate (%)

Graft loss to recurrence (%)

14-50 (average...
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

Graft survival according to primary disease

van Stralen Nephr...
Among 100 patients with SRNS…
~10% will be steroid resistant
One third are genetic Another third will recur post-Tx
Treatment options for recurrent FSGS

 High-dose iv CsA
 Plasmapheresis/immunoadsorption
 With or without iv CsA
 With...
Rituximab
375 mg/m² x 1-6

Sethna J Transplantation 2011
aHUS - Transplantation
aHUS is responsible for 2 to 5 % of children with ESRD
Overall recurrence rate: 50-60%
Median time ...
Tx options in aHUS

Noris Am J Transplant 2010
Eculizumab blocks terminal complement pathway
Ag-Ab complexes

Constitutive
Microorganisms

Lectin

Classical

Alternative...
In children, these diseases have a 80 to 100% risk
of recurrence in the renal graft

A.
B.
C.
D.
E.

Focal segmental glome...
In pediatric kidney Tx, the risk of malignancy is:

A.
B.
C.
D.
E.

Quite null
1 to 3% at 3 yrs
4 to 5% at 3 yrs
5 to 7% a...
Hospices Civils de Lyon & Université Claude-Bernard Lyon 1

The issue of malignancies
NAPRTCS 2010
Transplantation

POST T...
In pediatric kidney Tx, the risk of malignancy is:

A.
B.
C.
D.
E.

Quite null
1 to 3% at 3 yrs
4 to 5% at 3 yrs
5 to 7% a...
In children with a functioning renal graft, growth

A.
B.
C.
D.
E.

Returns to normal velocity
Is retarded in 10 to 20% of...
Fine Pediatr Nephrol 2009
Harambat Pediatr Nephrol 2009
In children with a functioning renal graft, growth

A.
B.
C.
D.
E.

Returns to normal velocity
Is retarded in 10 to 20% of...
Thank you for your attention!
9-1. Kidney transplantation in children. Pierre Cochat (eng)
9-1. Kidney transplantation in children. Pierre Cochat (eng)
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9-1. Kidney transplantation in children. Pierre Cochat (eng)

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9-1. Kidney transplantation in children. Pierre Cochat (eng)

  1. 1. pierre.cochat@chu-lyon.fr Centre de référence des maladies rénales rares Université de Lyon Kidney transplantation in children
  2. 2. The very first kidney transplantation in humans has been performed in A. B. C. D. E. Mumbai, India, 1915 Chicago, USA, 1912 Moskow, Russia, 1909 Lyon, France, 1906 London, UK, 1903
  3. 3. Pig-to-man kidney transplantation… Vascular anastomosis to the humeral vessels! Jaboulay Lyon Medical 1906
  4. 4. The first kidney transplantation in humans has been performed in A. B. C. D. E. Mumbai, India, 1915 Chicago, USA, 1912 Moskow, Russia, 1909 Lyon, France, 1906 London, UK, 1903
  5. 5. What is the lower age limit for kidney Tx? A. B. C. D. E. Birth 6 months 1 year 2 years 3 years
  6. 6. Indication for kidney transplantation  Children with irreversible renal failure  Minimal age: 6 to 12 mos  Minimal BW: 5 to 10 kg According to local experience & guidelines  Relative contraindications      ABO incompatibility Malignancy within the previous 12 months Active viral infection: HIV, VHB, VHC Active systemic disease: HUS, SLE, RPGN, vasculites, etc. Multiorgan failure, severe brain damage, etc.
  7. 7. Options according to age at start of RRT Age PD HD Tx Premature baby – Birth – 6 mos – 12 mos – 18 mos – 2 yrs
  8. 8. Transplantation 6 mos – 5.4 kg RRT options 1st yr of life Hemodialysis 5 mos – 4.8 kg Peritoneal dialysis 1000 g
  9. 9. NAPRTCS 2010
  10. 10. What is the lower age limit for kidney Tx? A. B. C. D. E. Birth 6 months 1 year 2 years 3 years
  11. 11. What is the part of pediatrics among all kidney Tx? A. B. C. D. E. 1% 2.5% 5% 7.5% 10%
  12. 12. Kidney transplantation activity in Europe Cochat Comprehensive Pediatric Nephrology 2008 Country Total Nb of Tx Tx in children (%) Croatia 109 4 (3.66%) Czech Republic 427 15 (3.51%) France 2423 81 (3.34%) Germany 2478 117 (4.72%) Israel 94 21 (22.3%) Italy 1746 58 (3.32%) Lithuania 63 2 (3.17%) Netherlands 420 14 (3.33%) Norway 256 9 (3.51%) Poland 1067 38 (3.56%) Spain 2057 68 (3.31%) Sweden 372 13 (3.49%) Turkey 665 59 (8.87%) UK 1516 128 (8.44%) 67 3 (4.47%) Serbia Average % Tx in children 4.5 %
  13. 13. What is the part of pediatrics among all kidney Tx? A. B. C. D. E. 1% 2.5% 5% 7.5% 10%
  14. 14. What is the main cause of ESRD in children < 5 yrs? A. B. C. D. E. CAKUT Steroid resistant nephrotic syndrome Inherited renal diseases Hemolytic uremic syndrome Chronic pyelonephritis
  15. 15. Wühl Clin J Am Soc Nephrol 2013
  16. 16. What is the main cause of ESRD in children < 5 yrs? A. B. C. D. E. CAKUT Steroid resistant nephrotic syndrome Inherited renal diseases Hemolytic uremic syndrome Chronic pyelonephritis
  17. 17. What are the 2 critically important outcomes in kidney Tx? A. B. C. D. E. Patient survival Blood pressure Graft survival Acute rejection Graft function
  18. 18. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 ERA-EDTA ERBP in press
  19. 19. What are the 2 critically important outcomes in kidney Tx? A. B. C. D. E. Patient survival Blood pressure Graft survival Acute rejection Graft function
  20. 20. Preemptive kidney Tx A. B. C. D. E. Is used for an average 25% of the pediatric population Is associated with a greater risk of nonadherence Can be proposed irrespective of the primary disease Provides the same survival than in dialysis children Relies on local facilities
  21. 21. % Preemptive Tx in Europe Cochat Comprehensive Pediatric Nephrology 2008 Sweden Norway Netherlands USA UK Spain Croatia France Germany Turkey Czech Rep Israel Serbia 0 10 20 30 40 50
  22. 22. Transplant characteristics in USA NAPRTCS 2007
  23. 23. The best option for RRT in children is preemptive Tx Dialysis should be limited to those children who cannot benefit from preemptive Tx Advantages  Avoids dialysis (school attendance, social and family life)  Avoids vascular/peritoneal access  Better results than non-preemptive Tx  Cost effectiveness Drawbacks  Timing for putting the patient on the waiting list?  Increased risk of non-adherence?
  24. 24. Preemptive kidney Tx A. B. C. D. E. Involves an average 25% of the pediatric population Is associated with a greater risk of nonadherence Can be proposed irrespective of the primary disease Provides the same survival than in dialysis children Relies on local facilities
  25. 25. In Europe, the average rate of living donation for children is A. B. C. D. E. 15% 20% 25% 30% 40%
  26. 26. % Living (related) donors in pediatric kidney Tx Cochat Comprehensive Pediatric Nephrology 2008 100 80 60 40 20 Sw USA itz er la n d Tu rk ey S Sc erb ia an di na via lan ds he r UK Ne t ae l Isr Sp ain Po lan d Fr an c Ge e rm an y Cr oa t ia Cz e ch Re p 0
  27. 27. In Europe, the rate of living donation for children is A. B. C. D. E. 15% 20% 25% 30% 40%
  28. 28. In the post-operative period after cadaver Tx, A. B. C. D. E. The use of 20% mannitol is recommended The use of dopamine at ‘renal’ dose enhances diuresis Urinary bladder catheter can be removed after 3 days IV wide-spectrum antibiotics should be given for 1 week A 2-week strict isolation period is mandatory
  29. 29. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 ERA-EDTA ERBP in press
  30. 30. In the post-operative period after cadaver Tx, A. B. C. D. E. The use of 20% mannitol is recommended The use of dopamine at ‘renal’ dose enhances diuresis Urinary bladder catheter can be removed after 3 days Antibiotic prophylaxis should be given for 1 week A 2-week strict isolation period is mandatory
  31. 31. The current rate of acute rejection in kidney Tx is: A. B. C. D. E. 3% 13% 23% 33% 43%
  32. 32. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 N Transplants with TheatissueRejection of ARE Least 1 N % N % 11519 All Transplants % 100.0 5846 100.0 5673 100.0 5256 45.6 2388 40.9 EXHIBIT 4.1A FREQUENCY OF ACUTE REJECTIONS 6263 54.4 3458 59.2 1987-2010 NAPRTCS 2010 2868 50.6 Transplantation Number of Acute Rejections 0 1 2 3 >4 Transplants with All Transplants at Least 1 Rejection Transplants withEra by Transplant at Least 1 Rejection 1987-1990 Number of Acute Rejections 1991-1994 0 1995-1998 1 1999-2002 2 2003-2006 3 2007-2010 >4 2805 49.4 2715 23.6 1289 22.1 1426 25.1 1253 10.9 597 10.2 656 11.6 Total 653 * 5.7 263 4.5 Living Donor 390 6.9 Deceased Donor 635 N 5.5 % 239 N 4.1 % 396 N 7.0 % 11519 100.0 5846 100.0 5673 100.0 5256 1509/2127 45.6 70.9 2388 593/908 40.9 65.3 2868 916/1219 50.6 75.1 1463/2413 6263 1126/2473 2715 653/2046 1253 394/1621 653 111/839 635 60.6 54.4 45.5 23.6 31.9 10.9 24.3 5.7 13.2 5.5 668/1198 3458 571/1362 1289 359/1239 597 163/808 263 34/331 239 55.8 59.2 41.9 22.1 29.0 10.2 20.2 4.5 10.3 4.1 795/1215 2805 555/1111 1426 294/807 656 231/813 390 77/508 396 65.4 49.4 50.0 25.1 36.4 11.6 28.4 6.9 15.2 7.0 Transplants with at Least 1 Rejection Total with known Era source (84 additional transplants have unknown donor source). by Transplant donor * 1987-1990 1509/2127 70.9 593/908 65.3 916/1219 75.1 1991-1994 NAPRTCS 2010 1463/2413 60.6 668/1198 55.8 795/1215 65.4 1995-1998 1126/2473 45.5 571/1362 41.9 555/1111 50.0
  33. 33. The current rate of acute rejection in kidney Tx is: A. B. C. D. E. 3% 13% 23% 33% 43%
  34. 34. In children, the main cause of graft failure is: A. B. C. D. E. Vascular thrombosis Recurrence of the primary disease Acute rejection Chronic rejection PTLD
  35. 35. NAPRTCS 2007
  36. 36. In children, the main cause of graft failure is: A. B. C. D. E. Vascular thrombosis Recurrence of the primary disease Acute rejection Chronic rejection (high rate of non-adherence) PTLD
  37. 37. In children, the risk of metabolic syndrome at 1 yr post-Tx is: A. B. C. D. E. 5 to 10% 15 to 20% 25 to 30% 35 to 40% 45 to 50%
  38. 38. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 Metabolic syndrome in children after renal Tx  Reversal of metabolic abnormalities depends on post-Tx GFR  But immunosuppressive drugs cause metabolic abnormalities  Atherosclerotic dyslipidemia  Insulin resistance  Risk of new-onset diabetes after Tx  Prevalence in children 1 year post-Tx: 35 to 40% (mostly de novo)  Major role of glucocorticoids  Falls to 5% in the absence of steroids  Greater risk of  Lower graft survival  Lower GFR  Left ventricular hypertrophy Litwin Pediatr Nephrol 2013
  39. 39. In children, the risk of metabolic syndrome at 1 yr post-Tx is: A. B. C. D. E. 5 to 10% 15 to 20% 25 to 30% 35 to 40% with steroid-based immunsuppression 45 to 50%
  40. 40. In children, the risk of metabolic syndrome at 1 yr post-Tx is: A. B. C. D. E. 5 to 10% without corticosteroids 15 to 20% 25 to 30% 35 to 40% 45 to 50%
  41. 41. Antibody-mediated rejection A. B. C. D. E. Is associated with serum donor-specific antibodies Can be treated by high-dose methylprednisolone Involves complement activation and endothelial injury Is characterized by peritubular capillary C4d staining Has better outcomes than cellular acute rejection
  42. 42. Humoral [antibody-mediated] rejection Diagnosis  Circulating anti-HLA Ab  Protocol biopsy (C4d)  Graft dysfunction Post Tx anti-HLA antibodies  DSA, donor specific antibodies     Blood transfusion Pregnancy Retransplantation DR matching
  43. 43. Pathology Pericapillary inflammation Courtesy Dr F Dijoud Lyon 2011 C4d+ on peritubular capillaries
  44. 44. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 Impact of donor-specific anti-HLA antibodies FO CUS O RENAL TRANSPLANTATIO N N 2005 Banff clasCAN as an entity se definition of ocesses that lead hy.25 Complement activation FO US O RENAL TRANSPLANTATIO C N N for this point of view grew and in the 2005 Banff clas- Circulating sification of renal allograft pathology, CAN as an entity Antibody-targeting DSAs therapies and was eliminated in favor of a more precise definition of the cellular and/or humoral rejection processes thathigh-dose IVIG lead Circulating DSAs to interstitial fibrosis and tubular atrophy.25 or ABMR Complement activation Acceleration of arteriosclerosis Antibody-targeting therapies and high-dose IVIG Current therapeutic approaches for ABMR Acceleration of arteriosclerosis MR are aimed at Endothelial injur y Current therapeutic approaches for ABMR are aimed at Endothelial injur y antibody reduction and the inhibition of complement of complement activation and injury. The available therapies include erapies include plasma exchange with low-dose IVIG, high-dose IVIG and rituximab for antibody reduction, and high-dose high-dose IVIG IVIG for complement inhibition. The activity of 2 and high-dose high-dose IVIG includes the inhibition of C3 convertase and the ability to absorb complement activation Figure 4 | DSA-mediated acceleration of arteriosclerosis. The presence of DSAs is The activity of fragments (such as C3a, C5a and C4b). Other, more associated with acceleration of arteriosclerosis after transplantation. This n of C3 converspecific, inhibitors of complement (such as eculizumab, phenomenon is observed in patients with either preformed/ persisting or de novo DSAs. The use of prophylactic anti-CD20 antibodies combined with high-dose IVIG an anti-C5 antibody) and inhibitors of C1 are likely to ment activation is associated presence of DSAs is Figure 4 | DSA-mediated acceleration of arteriosclerosis. Thewith lower grade arteriosclerosis 1 year after transplantation. show benefit in the prevention and treatment of ABMR. 33 Abbreviations: DSAs, donor-specific Human acceleration of kidney transplantation are trials of these drugs in arteriosclerosis after transplantation. This anti-HLA antibodies; IVIG, intravenous ). Other, more associated with immunoglobulin. now underway. h as eculizumab, phenomenonAis observedABO-incompatible transplantation in patients with either preformed/ persisting or de novo study of human published in 2012 showed anti-CD20 antibodies combined DSAs. The2012;of prophylactic that patients who received Conclusions with high-dose IVIG use Everly Transplantation 2013 Loupy Nat C1 are likely to Rev Nephrol 12 32,34 33 75 76–78 75 B-cell depletion with rituximab as an induction agent The increasing recognition of the frequency and diversity is associated with lower grade arteriosclerosis 1 year after transplantation.
  45. 45. Antibody-mediated rejection A. B. C. D. E. Is associated with serum donor-specific antibodies Can be treated by high-dose methylprednisolone Involves complement activation and endothelial injury Is characterized by peritubular capillary C4d staining Has better outcomes than cellular acute rejection
  46. 46. In children, these diseases have a 80 to 100% risk of recurrence in the renal graft A. B. C. D. E. Focal segmental glomerulosclerosis Atypical HUS with factor H mutation Primary hyperoxaluria type 1 Lupus nephritis MPGN type 2
  47. 47. Recurrent renal diseases: an overview Recurrence of the full primary renal disease High risk of graft loss Low risk of graft loss Late risk of graft loss Primary hyperoxaluria type 1 IgA nephropathy Type 1 diabetes Steroid resistant NS / FSGS Lupus nephritis Sickle cell disease Atypical HUS ANCA-associated GN Membranoproliferative GN Membranous nephropathy Recurrence of specific features Alloimmunization Urinary tract malformations Nephrin, Podocin Alport syndrome Posterior urethral valves Different from recurrence De novo renal diseases Specific deposits Membranous GN, TMA Cystinosis, Fabry
  48. 48. Recurrence rate after the 1st renal Tx Primary disease Recurrence rate (%) Graft loss to recurrence (%) 14-50 (average 30) 40-60 Atypical HUS 17 (MCP) – 90 (CFH-CFI) 10 (MCP) – 85 (CFH-CFI) Typical HUS 0-1 0-1 MPGN type 1 30-77 17-50 MPGN type 2 66-100 25-61 Lupus nephritis 0-30 0-5 IgAN (Berger disease) 32-60 3-7 Henoch Shönlein nephritis 31-100 8-10 Primary hyperoxaluria type 1 90-100 80-100 SRNS/FSGS Cochat Current Pediatr Rep 2013
  49. 49. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 Graft survival according to primary disease van Stralen Nephrol Dial Transplant 2013
  50. 50. Among 100 patients with SRNS…
  51. 51. ~10% will be steroid resistant
  52. 52. One third are genetic Another third will recur post-Tx
  53. 53. Treatment options for recurrent FSGS  High-dose iv CsA  Plasmapheresis/immunoadsorption  With or without iv CsA  With or without cyclophosphamide instead of MMF/Aza  Rituximab?
  54. 54. Rituximab 375 mg/m² x 1-6 Sethna J Transplantation 2011
  55. 55. aHUS - Transplantation aHUS is responsible for 2 to 5 % of children with ESRD Overall recurrence rate: 50-60% Median time to recurrence: 30 days [0 day – 16 yrs] Biological defect % of aHUS % disease recurrence % graft loss Factor H mutation 20-30 50-100 75-95 Anti-factor H antibodies 5-10 MCP/CD46 mutation 10-15 20 Factor I mutation 10-15 80-100 Factor B mutation <5 100 5-10 50 <5 5 30-40 60 ADAMTS-13 deficiency C3 mutation THBD (thrombomodulin) mutation No gene mutation 100 85 Kavanagh Semin Thromb Hemostasis 2010 - Loirat Pediatr Nephrol 2008 – Noris Am J Transplant 2010 – Sánchez-Corral Br J Haematol 2010
  56. 56. Tx options in aHUS Noris Am J Transplant 2010
  57. 57. Eculizumab blocks terminal complement pathway Ag-Ab complexes Constitutive Microorganisms Lectin Classical Alternative Terminal Proximal Microorganisms C3 C5a  Eculizumab binds with high affinity to C5  C3a C3b C5 Eculizumab Terminal complement activity is blocked  Proximal functions of complement remain intact  C5b C5b-9 Weak anaphylatoxin  Immune complex and apoptotic body clearance  Microbial opsonization Figueroa Clin Microbiol Rev 1991 - Walport N Engl J Med 2001
  58. 58. In children, these diseases have a 80 to 100% risk of recurrence in the renal graft A. B. C. D. E. Focal segmental glomerulosclerosis Atypical HUS with factor H mutation Primary hyperoxaluria type 1 Lupus nephritis MPGN type 2
  59. 59. In pediatric kidney Tx, the risk of malignancy is: A. B. C. D. E. Quite null 1 to 3% at 3 yrs 4 to 5% at 3 yrs 5 to 7% at 3 yrs 7 to 9% at 3 yrs
  60. 60. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1 The issue of malignancies NAPRTCS 2010 Transplantation POST TRANSPLANT MALIGNANCY RATE By Transplant Era 1 Year 3 Year % SE % SE 1987 – 1990 0.68 0.20 1.05 0.25 1991 – 1994 1.03 0.22 1.41 0.26 1995 – 1998 1.73 0.28 2.88 0.37 1999 – 2002 1.85 0.32 2.96 0.43 2003 - 2010 0.74 0.20 1.13 0.28 While substantial temporal improvements have been observed in graft failure, rejection and other endpoints, similar trends for malignancy rates were not observed, although the most recent cohort suggests that there has been some improvement. NAPRTCS 2010
  61. 61. In pediatric kidney Tx, the risk of malignancy is: A. B. C. D. E. Quite null 1 to 3% at 3 yrs 4 to 5% at 3 yrs 5 to 7% at 3 yrs 7 to 9% at 3 yrs
  62. 62. In children with a functioning renal graft, growth A. B. C. D. E. Returns to normal velocity Is retarded in 10 to 20% of patients Depends on steroid exposure Depends on GFR Can be improved by the use of rhGH
  63. 63. Fine Pediatr Nephrol 2009
  64. 64. Harambat Pediatr Nephrol 2009
  65. 65. In children with a functioning renal graft, growth A. B. C. D. E. Returns to normal velocity Is retarded in 10 to 20% of patients Depends on steroid exposure Depends on GFR Can be improved by the use of rhGH, if licenced
  66. 66. Thank you for your attention!

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